DNA damage in nasal and brain tissues of canines exposed to air pollutants is associated with evidence of chronic brain inflammation and neurodegeneration.

Acute, subchronic, or chronic exposures to particulate matter (PM) and pollutant gases affect people in urban areas and those exposed to fires, disasters, and wars. Respiratory tract inflammation, production of mediators of inflammation capable of reaching the brain, systemic circulation of PM, and disruption of the nasal respiratory and olfactory barriers are likely in these populations. DNA damage is crucial in aging and in age-associated diseases such as Alzheimer's disease. We evaluated apurinic/apyrimidinic (AP) sites in nasal and brain genomic DNA, and explored by immunohistochemistry the expression of nuclear factor NFkappaB p65, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX2), metallothionein I and II, apolipoprotein E, amyloid precursor protein (APP), and beta-amyloid(1-42) in healthy dogs naturally exposed to urban pollution in Mexico City. Nickel (Ni) and vanadium (V) were measured by inductively coupled plasma mass spectrometry (ICP-MS). Forty mongrel dogs, ages 7 days-10 years were studied (14 controls from Tlaxcala and 26 exposed to urban pollution in South West Metropolitan Mexico City (SWMMC)). Nasal respiratory and olfactory epithelium were found to be early pollutant targets. Olfactory bulb and hippocampal AP sites were significantly higher in exposed than in control age matched animals. Ni and V were present in a gradient from olfactory mucosa > olfactory bulb > frontal cortex. Exposed dogs had (a) nuclear neuronal NFkappaB p65, (b) endothelial, glial and neuronal iNOS, (c) endothelial and glial COX2, (d) ApoE in neuronal, glial and vascular cells, and (e) APP and beta amyloid(1-42) in neurons, diffuse plaques (the earliest at age 11 months), and in subarachnoid blood vessels. Increased AP sites and the inflammatory and stress protein brain responses were early and significant in dogs exposed to urban pollution. Oil combustion PM-associated metals Ni and V were detected in the brain. There was an acceleration of Alzheimer's-type pathology in dogs chronically exposed to air pollutants. Respiratory tract inflammation and deteriorating olfactory and respiratory barriers may play a role in the observed neuropathology. These data suggest that Alzheimer's disease may be the sequela of air pollutant exposures and the resulting systemic inflammation.

Respiratory damage in children exposed to urban pollution.

Southwest Metropolitan Mexico City (SWMMC) children are chronically exposed to complex mixtures of air pollutants. In a cross-sectional arm of our study, we investigated the association between exposure to SWMMC atmosphere and nasal abnormalities, hyperinflation, and interstitial markings assessed by chest X-rays, lung function changes, several serum cytokines, and endothelin-1 in 174 children aged 5-17 years vs. 27 control children residents in low-polluted areas. Control children had no nasal lesions, and only one child showed an abnormal chest X-ray. SWMMC children exhibited nasal abnormalities (22%), hyperinflation (67%), interstitial markings (49%), and a mild restrictive pattern by spirometry (10%). Interstitial markings were associated with a decrease in predicted values of FEF(25-75), FEF(75), and the FEV(1)/FVC ratio. Boys had a higher probability of developing interstitial markings with age (P = 0.004). Blood smear findings included toxic granulations in neutrophils and schistocytes. SWMMC children had more serum IL10 and IL6 and less IL8 than controls. In a longitudinal arm of our study, we found a significant seasonal drop in FVC and FEV(1) associated with a 6-month period of high ozone and PM(10) levels. Our data strongly suggest that a lifelong exposure to urban air pollution causes respiratory damage in children. Moreover, a cytokine network becomes imbalanced, with a shift towards upregulation of anti-inflammatory cytokines. Consequently, these children are potentially at risk for developing chronic lung disease and other systemic effects later in life.

Air pollution and brain damage.

Exposure to complex mixtures of air pollutants produces inflammation in the upper and lower respiratory tract. Because the nasal cavity is a common portal of entry, respiratory and olfactory epithelia are vulnerable targets for toxicological damage. This study has evaluated, by light and electron microscopy and immunohistochemical expression of nuclear factor-kappa beta (NF-kappaB) and inducible nitric oxide synthase (iNOS), the olfactory and respiratory nasal mucosae, olfactory bulb, and cortical and subcortical structures from 32 healthy mongrel canine residents in Southwest Metropolitan Mexico City (SWMMC), a highly polluted urban region. Findings were compared to those in 8 dogs from Tlaxcala, a less polluted, control city. In SWMMC dogs, expression of nuclear neuronal NF-kappaB and iNOS in cortical endothelial cells occurred at ages 2 and 4 weeks; subsequent damage included alterations of the blood-brain barrier (BBB), degenerating cortical neurons, apoptotic glial white matter cells, deposition of apolipoprotein E (apoE)-positive lipid droplets in smooth muscle cells and pericytes, nonneuritic plaques, and neurofibrillary tangles. Persistent pulmonary inflammation and deteriorating olfactory and respiratory barriers may play a role in the neuropathology observed in the brains of these highly exposed canines. Neurodegenerative disorders such as Alzheimer's may begin early in life with air pollutants playing a crucial role.

Assessment of physical education time and after-school outdoor time in elementary and middle school students in south Mexico City: the dilemma between physical fitness and the adverse health effects of outdoor pollutant exposure.

Strategies to promote lifelong physical activity among children are needed to stem the adverse health consequences of inactivity. However, the health effects in growing children of long-term exposure to a polluted atmosphere are of deep concern. The atmosphere of south Mexico City (SMC) is characterized by a complex mixture of air pollutants, including ozone, particulate matter, and aldehydes. Radiological evidence suggests that small-airway disease could be present in clinically healthy, tobacco unexposed SMC children. The aim of this study was to assess, by means of a self-reported questionnaire, the physical education class times, daily outdoor after-school exposure time, and tobacco exposure in students attending public elementary and middle schools in SMC. Additionally, the time each student spent viewing television was assessed, and the authors measured each student's weight and height to determine body mass index (BMI, weight in kg divided by height in m2). The survey included 1,159 students in grades 7-9. The authors identified 2 critical periods of outdoor exposure in SMC children that coincided with significant concentrations of both ozone and particulate matter with diameters less than 10 micrometers (PM10): during school time after 11:00 A.M. and in the after-school outdoor activity period, usually extending from 1:00 P.M. to 6:00 P.M. Thirty-two percent of elementary and 61% of middle school students have physical education classes after 11:00 A.M. Students in SMC spend an average of 19.6 hr/wk outdoors in the after-school period, during which time they are engaged in light to moderate physical activities. Half of the students are exposed to tobacco smoke at home, and 7% of middle school students smoke. On the basis of BMI, 60% of students were classified as undernourished, overweight, or obese. No correlations were found between BMI and time spent viewing TV, time outdoors (on weekdays and weekends), or exposure to environmental tobacco smoke. Children and adolescents in SMC are participating in physical activities that enhance multiple components of health-related fitness. However, their activities occur outdoors, where they are exposed to high concentrations of air pollutants throughout the year. The authors believe that SMC children and adolescents must be educated, through both the school and health systems, regarding ways to obtain the necessary exercise while protecting themselves from the high concentrations of pollutants. Individuals should instruct and encourage young people to be involved in lifetime fitness activities and to eat balanced diets, if the goal is to control health-care costs, reduce disease incidence, and improve the overall quality of life of the Mexico City population.